This review discusses the concepts and methods for assessing patient adherence to treatment, as applied to both epidemiological and clinical approaches within real health care practices. For the epidemiological approach, the assessment must be as accurate as possible. Self-reported questionnaires are the most feasible option in most circumstances, but most demonstrate low sensitivity combined with high specificity. We suggest that self-reported outcomes, where feasible, can increase the sensitivity for non-adherence of these questionnaires. In the clinical approach an accurate distinction between adherents and non-adherents is less useful. For the health provider, it is more important to be aware of the particular situation that each patient is currently experiencing with his/her treatment. Self-reported questionnaires applied in clinical settings can help the health provider to form an objective opinion. In any event, the patient-provider dialogue is still the best approach to assess patient adherence as well as to deliver good care.